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Mini-plasminogen-like fragments of plasminogen in synovial fluid in acute inflammatory arthritis
Abstract:
Neutrophil elastase digests plasminogen to yield a fragment, mini-plasminogen, which is activatable to a mini-plasmin capable of escaping the action of the primary plasmin inhibitor. Such a molecule may play a role in joint destruction, either directly or by activation of procollagenase to collagenase. Synovial fluid samples from 34 acute joint effusions were examined by lysine-Sepharose chromatography and fibrinolytic assay of the fall-through (non-lysine-binding) fractions in presence of urokinase. Fragments similar to mini-plasminogen were found in 20 of 23 inflammatory effusions (cell count greater than 0.5 X 10(3)/microliter) and in none of 11 non-inflammatory (traumatic and osteoarthritic) effusions (cell count less than 0.5 X 10(3)/microliter) (p less than 0.001). Analysis of four inflammatory fluids by gel filtration on Bio-Gel P 100 and enzyme-linked immunoassay for plasminogen antigen revealed plasminogen fragments with molecular weight similar to mini-plasminogen (34,000 daltons) in three, and larger plasminogen fragments (or complexes of mini-plasminogen with other synovial fluid macromolecules) in all four. Fibrinolytic activity was demonstrable in fractions containing plasminogen fragments after treatment with tissue type plasminogen activator. In contrast with non-inflammatory effusions, inflammatory joint fluids contain plasminogen fragments with the properties of mini-plasminogen, suggesting their possible role in inflammatory joint destruction.
Insights
Inflammatory joint effusions contain plasminogen fragments, termed mini-plasminogen, which may contribute to joint destruction. These fragments, generated by neutrophil elastase, are found in inflammatory but not non-inflammatory joint fluids.
Area of Science:
- Biochemistry
- Rheumatology
- Molecular Biology
Background:
- Neutrophil elastase (NE) degrades plasminogen into mini-plasminogen (mPLG).
- Mini-plasminogen can activate to mini-plasmin, evading primary plasmin inhibitor.
- This process may contribute to joint destruction via direct action or collagenase activation.
Purpose of the Study:
- To investigate the presence and properties of plasminogen fragments in synovial fluid from acute joint effusions.
- To determine if these fragments are associated with inflammatory versus non-inflammatory joint conditions.
Main Methods:
- Lysine-Sepharose chromatography and fibrinolytic assays were used on synovial fluid.
- Urokinase and tissue plasminogen activator (t-PA) were employed for activation studies.
- Gel filtration and enzyme-linked immunosorbent assay (ELISA) were used for fragment characterization.
Main Results:
- Mini-plasminogen-like fragments were detected in 20/23 inflammatory effusions but none of 11 non-inflammatory effusions (p < 0.001).
- Analysis revealed fragments similar in molecular weight to mini-plasminogen (34 kDa) and larger fragments/complexes.
- Fibrinolytic activity was observed in fractions containing these fragments upon t-PA treatment.
Conclusions:
- Inflammatory joint fluids contain plasminogen fragments with mini-plasminogen properties.
- These fragments are significantly associated with inflammatory joint effusions.
- The findings suggest a potential role for mini-plasminogen in the pathogenesis of inflammatory joint destruction.